The steroid/thyroid hormone receptor super-family consists of regulatory proteins which play important roles in many aspects of gene control and cell signalling pathways. We have identified a DNA-binding protein (named CERF) which interacts with a negative regulatory element in the promoter region of the chicken GATA-1 gene. The CERF protein is likely to be related to the Drosophila ecdysone receptor, as the binding site and specificity of the two proteins is identical. The GATA-1 transcription factor is a nuclear protein that regulates the expression of erythroid- specific genes, and is believed to be a major determinant of erythroid cell identity during early vertebrate development. We propose to study the role of CERF during development and in the regulation of the cGATA-1 gene. We also propose to isolate the cDNA encoding CERF protein; the various methods we will use should identify other factors related to the ecdysone receptor and other putative orphan receptors of the thyroid hormone receptor family. We anticipate that studying CERF might yield new information concerning signal transduction via orphan receptors with particular impact on the process of cellular determination and differentiation.